Synthesis and anticancer activity of oxindole derived imidazo[1,5-a]pyrazines

A series of oxindole derivatives of imidazo[1,5-a]pyrazines were prepared and confirmed by 1H NMR, mass and HRMS data. These compounds were evaluated for their anticancer activity against a panel of 52 human tumor cell lines derived from nine different cancer types: leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast. Among them compound 7l showed significant anticancer activity with GI50 values ranging from 1.54 to 13.0 μM. Cell cycle arrest was observed in G0/G1 phase upon treatment of A549 cells with 6.5 μM (IC50) concentration of compound 7l and induced apoptosis. This was confirmed by Annexin V-FITC as well as DNA fragmentation analysis and interestingly this compound (7l) did not affect the normal cells.     

Synthesis and apoptosis inducing ability of new anilino substituted pyrimidine sulfonamides as potential anticancer agents

A series of anilino substituted pyrimidine sulfonamides were prepared and evaluated for their anticancer activity. These sulfonamides showed promising activity with IC₅₀ values ranging from 5.6 to 12.3 μM. The detailed biological aspects of some of the promising compounds (3d, 3e and 3g) on the K562 cell line were studied. Interestingly, compounds induced G1 cell cycle arrest and down regulation of G1 phase cell cycle regulatory proteins such as cyclin D1, CDK4. These compounds also exhibited inhibition of NF-κB as well as its downstream target gene Akt1 and the phosphorylated form of AKt ser 474 proteins. One of the representative compound 3e could be considered as the potential lead for its development as a new anticancer agent.     

Synthesis and biological evaluation of some 4-functionalized-pyrazoles as antimicrobial agents

1,3-Diaryl-4-formylpyrazoles 8 bearing benzenesulfonamide moiety at position-1 were synthesized as important intermediates following Vilsmeier-Haack strategy. Aldehyde moiety of 4-formylpyrazole was then converted into carboxylic acid 9, cyano 10 and carbothioamide 11 using established procedures. Out of these 4-functionalized pyrazoles, pyrazole-4-carboxylic acids 9 and carbothioamides 11 were evaluated for their in vitro antibacterial activity against four pathogenic bacterial strains namely, Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and in vitro antifungal activity against two pathogenic fungal strains namely, Aspergillus niger and Aspergillus flavus. Three tested compounds, 9e, 11b and 11f exhibited moderate antibacterial activity against Gram-positive bacteria and 9g showed moderate antifungal activity against the tested fungi. However, none of the compounds showed any activity against Gram-negative bacteria.     

Cerebrospinal fluid lactate: Is it a reliable and valid marker to distinguish between acute bacterial meningitis and aseptic meningitis?

Cerebrospinal fluid (CSF) lactate assay has been a subject of research since 1925. A systematic review by Huy and colleagues in the previous issue of Critical Care summarizes data from 25 studies evaluating the role of CSF lactate in the differential diagnosis between acute bacterial and aseptic meningitis. The authors concluded that CSF lactate is a good single indicator and a better marker compared with conventional markers. But concerns remain because of poor quality of included studies, lack of proper 'gold standard', and limited applicability. More studies with a rigorous design are needed to determine definitively whether CSF lactate assay is a reliable and valid marker to distinguish between acute bacterial meningitis and aseptic meningitis.     

Active scaffolds for on-demand drug and cell delivery

Porous biomaterials have been widely used as scaffolds in tissue engineering and cell-based therapies. The release of biological agents from conventional porous scaffolds is typically governed by molecular diffusion, material degradation, and cell migration, which do not allow for dynamic external regulation. We present a new active porous scaffold that can be remotely controlled by a magnetic field to deliver various biological agents on demand. The active porous scaffold, in the form of a macroporous ferrogel, gives a large deformation and volume change of over 70% under a moderate magnetic field. The deformation and volume variation allows a new mechanism to trigger and enhance the release of various drugs including mitoxantrone, plasmid DNA, and a chemokine from the scaffold. The porous scaffold can also act as a depot of various cells, whose release can be controlled by external magnetic fields.     

Environmental factors associated with Crohn’s disease in India

Background  

The frequency of diagnosis of Crohn’s disease (CD) in India is increasing. This case-control study was designed to detect associations of environmental and dietary factors with the diagnosis of CD.     

Cutaneous mucormycosis with necrotising fasciitis in a young immunocompetent individual

Primary cutaneous mucormycosis is uncommon and is extremely rare in immunocompetent young individuals. Here we report a case of necrotising fasciitis due to mucormycosis in an immunocompetent young individual following minor trauma. Mucormycosis must be suspected in any wound that is worsening despite appropriate treatment even in immunocompetent individuals.